Our overall aim is to identify and characterize genetic differences that are important to the human response to infection and inflammation. First, we will use in vivo and in vitro models of inflammation to determine the functional impact of single nucleotide polymorphisms (SNPs) in inflammation-related genes. Second, we propose to identify SNPs that will help characterize an individual patient's risk for severe infection and death after injury. This information will allow clinicians and researchers to more rationally investigate and use specific therapies aimed at reducing the devastating consequences of severe injury and infection.